Although transcranial direct current stimulation (tDCS) has been used in the treatment of epilepsy for many years, further research is needed on the efficacy and safety of tDCS treatment. This systematic review and meta-analysis aimed to explore the effectiveness of tDCS on seizure frequency (SF), epileptiform discharges, depression, anxiety, and cognitive function in epilepsy.

We searched the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases from inception to 9 September 2024. The primary outcomes included SF. The secondary outcomes included epileptiform discharges, depression, anxiety, cognitive function, and adverse events. The meta-analysis was conducted using Review Manager 5.4 software.

12 trials were included, 356 participants (219 in the tDCS group and 137 in the sham group). Among the included studies, three were of high risk, two were of some concern, and seven were of low risk. For the primary outcome metrics, tDCS can reduce the frequency of epileptic seizures (SMD = - 0.63, 95 % CI = [-0.90, - 0.36], P < 0.00001). For secondary outcome measures, there are no statistical differences between the tDCS group and the sham group in epileptiform discharges (SMD = - 0.27, 95 % CI = [-0.71, 0.16], P = 0.22) and adverse events (MD = 1.30, 95 % CI = [0.49, 3.45], P = 0.60). The outcomes of tDCS treatment for depression and anxiety were inconsistent. tDCS did not enhance or impair cognitive function.

tDCS can reduce SF but has no effect on epileptiform discharges in patients with epilepsy. The current evidence is limited to support tDCS treatment for depression, anxiety, and cognitive function in epilepsy patients. Future studies should be standardized and personalized, ensure higher methodological rigor, and probe long-term effects to prove the findings further.

Reproduction is lower in male individuals compared with female individuals with epilepsy. The reason is unknown. We studied sex-specific reproduction in individuals with epilepsy and the role of epilepsy subtype and psychiatric comorbidity.

We conducted a population-based register study in Denmark, using data from January 1, 1982, to December 31, 2021. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs for the chance of having ≥1 child. We followed all persons from 15 years of age until birth of live-born offspring, 45 years of age, emigration, death, or end of follow-up (December 31, 2021), whichever occurred first. Epilepsy status was identified from the Danish National Patient Register. The primary outcome was the occurrence of live-born children identified from the Danish Medical Birth Register among persons with and without epilepsy.

We included 2,593,097 individuals (49% of female individuals), including 46,243 (1.8%) with epilepsy (mean age at diagnosis of 13.1 years [SD 9.2]). Compared with individuals without epilepsy, the aHR of having ≥1 child was reduced in both sexes with epilepsy, but lower in male individuals (0.59, 95% CI 0.57-0.60) compared with female individuals with epilepsy (0.72, 95% CI 0.71-0.74). By age 45 years, the probability of being childless was 45.9% in male individuals and 30.7% in female individuals with epilepsy, compared with 22.8% in male individuals and 14.1% in female individuals without epilepsy. Compared with persons without epilepsy, the chance of having a first child was lower in female individuals with focal epilepsy (aHR 0.61, 95% CI 0.58-0.64) than in female individuals with generalized epilepsy (aHR 0.72, 95% CI 0.69-0.75), and lower in male individuals with focal epilepsy (aHR 0.51, 95% CI 0.48-0.53) than in male individuals with generalized epilepsy (aHR 0.57, 95% CI 0.54-0.60). Reproduction was particularly low in persons with epilepsy and psychiatric comorbidity (male individuals: aHR 0.30, 95% CI 0.28-0.32; female individuals: aHR 0.51, 95% CI 0.48-0.53).

Individuals with epilepsy were less likely to become parents than individuals without epilepsy, and the association was stronger in male individuals and those with psychiatric comorbidity and varied with epilepsy subtype.

Cognitive and behavioral comorbidity is frequent in childhood epilepsy and impacts on prognosis and QOL. Comorbidity often precedes seizure onset. Early screening is recommended but no consensus exists on the screening method. The current pilot study investigated the feasibility and validity of a newly developed screening method in children with recently diagnosed epilepsy.

An online screening method was developed using a combination of existing and validated screening instruments (i.e. 2 standardised questionnaires and 2 psychometric tests), selected to detect the most common comorbid problems in childhood epilepsies. Feasibility was studied using patient and parent questionnaires and drop-out rates. Validity was studied by comparing the screening results to an in-depth diagnostic assessment. Descriptive statistics were used to analyse results.

Out of twenty referred children, 13 entered the study, of whom 1 dropped out (retention rate 93 %). Of those, ten were girls. Most patients were aged 9-12 year (38 %) or 12-15-year (38 %). Eighty-three percent of tested children proved to have cognitive or behavioral comorbidity. Screening results corresponded with diagnostic assessment results in most cases (9 true positives, one true negative), there was 1 false positive and 1 false negative screening result. Sensitivity of the screening amounts to 90 % (CI 73-107).

The current pilot study shows promising results with regards to feasibility and validity of the tested screening method for cognitive and behavioral comorbidity in childhood epilepsy. This warrants further investigation of the method.

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

Evidence suggests that anthropogenic climate change is accelerating and is affecting human health globally. Despite urgent calls to address health effects in the context of the additional challenges of environmental degradation, biodiversity loss and ageing populations, the effects of climate change on specific health conditions are still poorly understood. Neurological diseases contribute substantially to the global burden of disease, and the possible direct and indirect consequences of climate change for people with these conditions are a cause for concern. Unaccustomed temperature extremes can impair the systems of resilience of the brain, thereby exacerbating or increasing susceptibility to neurological disease. In this Perspective, we explore how changing weather patterns resulting from climate change affect sleep - an essential restorative human brain activity, the quality of which is important for people with neurological diseases. We also consider the pervasive and complex influences of climate change on two common neurological conditions: stroke and epilepsy. We highlight the urgent need for research into the mechanisms underlying the effects of climate change on the brain in health and disease. We also discuss how neurologists can respond constructively to the climate crisis by raising awareness and promoting mitigation measures and research - actions that will bring widespread co-benefits.

Epilepsy presents multifaceted challenges, including sexual dysfunction and psychiatric comorbidities in men. Understanding the interplay between epilepsy, antiseizure medications, hormonal alterations, and sexual dysfunction is crucial for tailored interventions and improved quality of life.

This case-control study enrolled 226 married men (150 MWE, 76 controls) from a tertiary care neurology hospital in Southern India. Demographic, clinical, and hormonal data were collected. Sexual dysfunction was assessed using the Arizona Sexual Experience Scale (ASEX) and the Premature Ejaculation Diagnostic Tool (PEDT). Psychiatric symptoms were evaluated using the DASS-21 questionnaire.

Nineteen percent of MWE exhibited significant sexual dysfunction. Median ASEX scores were significantly higher in polytherapy (15) compared with monotherapy (13) and controls (10), (p < 0.0001). The cut-off score for sexual dysfunction (>18) was present in 20 individuals in the polytherapy group, 8 in the monotherapy group and none in the control group (p < 0.0001). PEDT scores showed a similar pattern, with statistically significant differences between subgroups. Hormonal analysis revealed dysregulated LH and testosterone levels in MWE and were significantly more on pairwise comparisons in the polytherapy subgroup. Epilepsy duration, valproate usage, and presence of anxiety/depression were associated with sexual dysfunction on a multivariable regression model using the Akaike information criterion.

This study elucidates the complex relationship between epilepsy, medications, hormonal alterations, and sexual dysfunction in men. Valproate was found to be strongly associated with sexual dysfunction and hormonal imbalance. Further research is warranted to address study limitations and advance our understanding of sexual dysfunction in MWE.

Cenobamate (CNB) is an anti-seizure medication (ASM) utilized for drug-resistant focal-onset seizures, which are difficult to manage with usual agents. Previous studies demonstrated that it can be effective in patients with refractory epilepsy.

The MEDLINE, Cochrane, and Scopus databases were systematically searched up to 24 October 2024. A Random-effects model was employed to compute the Mean Difference (MD) and the Risk Ratio (RR) with 95% Confidence Intervals (CI). Statistical Analyses were performed utilizing RStudio 4.4.2.

Four studies were included, comprising 906 patients; 527 (59%) received CNB as add-on therapy. The results indicated that the 50% responder rate (RR 1.77; 95% CI: 1.28 to 2.44, p = 0.000551, I² = 70.3%) and seizure freedom (RR of 3.09; 95% CI: 1.91 to 5.00, p = 0.000004, I² = 8.7%) were significantly higher in this group.

In this meta-analysis of four studies, CNB as an add-on therapy significantly reduced seizure frequency in patients with uncontrolled focal seizures, making it a promising option for improved seizure control and quality of life.

Epilepsy, one of the most common neurological diseases, affects more than 70 million people worldwide. Anti-seizure drugs targeting membrane ion channels or GABAergic neurotransmission are the first choices for controlling seizures, whereas the high incidence of pharmacoresistance and adverse effects largely restrict the availability of current anti-seizure drugs (ASDs). Traditional Chinese Medicine (TCM) has shown historical evidence-based therapeutic effects for neurological diseases including epilepsy. But until the late 1990s, great efforts in both clinical and experimental fields advanced TCM interventions for epilepsy from evidence-based practices to more systematic neuropharmacological significance, and show new lights on preferable management of epilepsy in the last decade. This review summarized the advances of applying TCM interventions (ranging from herbal medicines and their active ingredients to other strategies such as acupuncture) for epilepsy, followed by associated mechanism theories. The therapeutic potential of TCM interventions for epilepsy as well as its comorbidities turns from somehow debatable to hopeful. Finally, some prospects and directions were proposed to drive further clinical translational research. The future directions of TCM should aim at not only deriving specific anti-epileptic molecules but also illustrating more precise mechanisms with the assistance of advanced multifaceted experimental tools.

This study aims to evaluate the changes in the functional brain networks and graph theory analysis of patients with epilepsy and comorbid migraine without aura (EM).

We included 30 patients with EM, 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. Resting-state functional magnetic resonance imaging was performed to obtain imaging data.

The fractional amplitude of low-frequency fluctuations (fALFF) value of the left superior temporal gyrus was higher in the EM group than in the HC group. The regional homogeneity (ReHo) values of the right orbital superior frontal gyrus were higher in the EM group than in the EC group. The functional connectivity between left superior occipital gyrus and left orbital part of the superior frontal gyrus, left middle temporal gyrus, right orbital part of middle frontal gyruss, left medial superior frontal gyrus (cluster 2), right middle frontal gyrus, left middle frontal gyrus, left median cingulate and paracingulate gyri was enhanced in the EM group compared with the HC group; the functional connectivity between the left superior occipital and left medial superior frontal gyri (cluster 1) was weakened. The functional connectivity was weakened between the posterior default mode network (pDMN) and dorsal sensorimotor network (dSMN) and the left frontoparietal network (LFPN) and right frontoparietal network. The functional connectivity between pDMN and LFPN was enhanced in the EM group compared with the EC group. Graph theory analysis revealed that the area under the curve of the standardized characteristic path length of the EM group was smaller than that of the HC and EM groups.

The abnormal functional brain networks associated with pain regulation, and changes in topological properties may be involved in the mechanisms underlying migraine without aura occurrence in patients with epilepsy.

The interactions of anxiety, depression, and the quality of life (QOL) in people with epilepsy (PWE) are unclear. This research aimed to explore how anxiety and depression interact to influence QOL.

The QOL, anxiety and depression of 1162 PWE were investigated via questionnaires and 849 of PWE were finally used in the statistical analyses. Mediation analysis was conducted to analyzed the mediating effect of depression in the relationship between anxiety and QOL.

849 PWE with a mean age of 46.62 ± 14.01 (range, 18-85) years were included finally, and 61.2 % were male. Mediation analysis revealed that depression indirectly mediated the relationship between anxiety and QOL (B = -0.445, bootstrap 95 % CI = -0.497 to -0.394). On the total score and the six out of seven domains of QOLIE-31 (seizure worry, overall QOL, emotional well-being, energy/fatigue, cognitive function, and social function), the indirect effect of depression (range, 51.0 %-68.9 %) are exceeded the direct effect of anxiety. Concerning the "medication effect", the indirect effect (36.0 %) of depression is smaller.

The effect of anxiety on QOL is mainly explained by the partial mediation of depression. Specifically, anxiety primarily affects QOL through the effect of depression on the total QOL score and the other six domains. However, the direct effect of anxiety was stronger for the medication effect domain.

The primary objective of this exploratory study was to examine the current situation of people with epilepsy (PWE) in the German labor market and how epilepsy affects their daily working life.

From June 2023 to March 2024, we conducted an exploratory online survey in adult PWE in Germany.

The online survey was completed by 193 PWE (median age: 40.5 years; Q25/75: 27/53; 62 % female). The participants reported the following effects of their diagnosis on their professional lives: Experiencing reduced work performance due to perceived adverse drug reactions (102/193; 53 %), worrying often about the professional future (93/193; 48 %), and perceiving every-day work or school life to be more challenging because of the diagnosis (90/193; 47 %). Of the 81 participants who were diagnosed before finishing school, 26/81 (32 %) could not pursue their initial career aspirations after receiving their diagnosis. Of the PWE who were diagnosed during their vocational or academic training, 3/35 (9 %) had to specialize differently in their field of training, and 10/35 (29 %) were forced to stop their training. 10/77 (13 %) PWE who were diagnosed during their professional life could not keep their job following the diagnosis.

According to self-reports, one of the main challenges faced by adult PWE is the deterioration of work performance due to perceived adverse drug reactions. They also perceived a major mental strain regarding their professional future because of the diagnosis. Moreover, they felt considerably limited in their career choices, especially if they were diagnosed early in life.

The aim was to examine the personal impact of epilepsy on well-being, and influencing factors in individuals with epilepsy.

This cross-sectional descriptive study was conducted on 138 individuals with epilepsy. Data were collected using the "Descriptive Information Form," the "Personal Impact of Epilepsy Scale (PIES)," and the "World Health Organization-Five Well-Being Index (WHO-5)". In the statistical analysis, p < 0.05 was considered significant.

The mean age of individuals with epilepsy was 31.22 ± 13.12 years, and the mean duration of epilepsy diagnosis was 9.93 ± 6.84 years. The mean WHO-5 Well-Being Index score was 62.55 ± 26.26 and the mean PIES scale score was 34.27 ± 20.27. According to the regression analysis results, well-being (β = -0.568; p = 0.000) and the duration of epilepsy diagnosis (β = -0.130; p = 0.041) were negative predictors, while the number of seizures (β = 0.209; p = 0.001) and age (β = 0.180; p = 0.010) were positive predictors of PIES. This explained 52.8 % of the total PIES score.

The well-being of individuals with epilepsy was found to be above average, and the personal impact of epilepsy was found to be low. Low well-being of individuals with epilepsy increased the negative impact of epilepsy on the individual. Number of seizures, older age, and the shortness of the diagnosis period negatively affected the individual with epilepsy personally. Health professionals need to focus on the influencing factors of individuals with epilepsy to increase their well-being and reduce the negative effects of epilepsy.

Scalp electroencephalography (EEG) is a cornerstone in the diagnosis and treatment of epilepsy, but routine EEG is often interpreted as normal without identification of epileptiform activity during expert visual review. The absence of interictal epileptiform activity on routine scalp EEGs can cause delays in receiving clinical treatment. These delays can be particularly problematic in the diagnosis and treatment of people with drug-resistant epilepsy (DRE) and those without structural abnormalities on MRI (i.e., MRI negative). Thus, there is a clinical need for alternative quantitative approaches that can inform diagnostic and treatment decisions when visual EEG review is inconclusive. In this study, we leverage a large population-level routine EEG database of people with and without focal epilepsy to investigate whether normal interictal EEG segments contain subtle deviations that could support the diagnosis of focal epilepsy.

We identified multiple epochs representing eyes-closed wakefulness from 19-channel routine EEGs of a large and diverse neurological patient population (N=13,652 recordings, 12,134 unique patients). We then extracted the average spectral power and phase-lag-index-based connectivity within 1-45Hz of each EEG recording using these identified epochs. We decomposed the power spectral density and phase-based connectivity information of all the visually reviewed normal EEGs (N=6,242) using unsupervised tensor decompositions to extract dominant patterns of spectral power and scalp connectivity. We also identified an independent set of routine EEGs of a cohort of patients with focal epilepsy (N= 121) with various diagnostic classifications, including focal epilepsy origin (temporal, frontal), MRI (lesional, non-lesional), and response to anti-seizure medications (responsive vs. drug-resistant epilepsy). We analyzed visually normal interictal epochs from the EEGs using the power-spectral and phase-based connectivity patterns identified above and evaluated their potential in clinically relevant binary classifications.

We obtained six patterns with distinct interpretable spatio-spectral signatures corresponding to putative aperiodic, oscillatory, and artifactual activity recorded on the EEG. The loadings for these patterns showed associations with patient age and expert-assigned grades of EEG abnormality. Further analysis using a physiologically relevant subset of these loadings differentiated patients with focal epilepsy from controls without history of focal epilepsy (mean AUC 0.78) but were unable to differentiate between frontal or temporal lobe epilepsy. In temporal lobe epilepsy, loadings of the power spectral patterns best differentiated drug-resistant epilepsy from drug-responsive epilepsy (mean AUC 0.73), as well as lesional epilepsy from non-lesional epilepsy (mean AUC 0.67), albeit with high variability across patients.

Our findings from a large population sample of EEGs suggest that normal interictal EEGs of patients with epilepsy contain subtle differences of predictive value that may improve the overall diagnostic yield of routine and prolonged EEGs. The presented approach for analyzing normal EEGs has the capacity to differentiate several diagnostic classifications of epilepsy, and can quantitatively characterize EEG activity in a scalable, expert-interpretable, and patient-specific fashion. Further technical development and clinical validation may yield normal EEG-derived computational biomarkers that could augment epilepsy diagnosis and assist clinical decision-making in the future.

The problem of drug resistance in epilepsy means that in many cases, a surgical treatment may be advised. But this is only possible if there is an epileptic focus, and resective brain surgery may have adverse side effects. One of the promising alternatives is gene therapy, which allows the targeted expression of therapeutic genes in different brain regions, and even in specific cell types. In this review, we provide detailed explanations of some key terms related to genetic engineering, and describe various regulatory elements that have already been used in the development of different approaches to treating epilepsy using viral vectors. We compare a few universal promoters for their strength and duration of transgene expression, and in our description of cell-specific promoters, we focus on elements driving expression in glutamatergic neurons, GABAergic neurons and astrocytes. We also explore enhancers and some other cis-regulatory elements currently used in viral vectors for gene therapy, and consider future perspectives of state-of-the-art technologies for designing new, stronger and more specific regulatory elements. Gene therapy has multiple advantages and should become more common in the future, but there is still a lot to study and invent in this field.

There is accumulating evidence suggesting a connection between epilepsy, a neurologic disease with recurrent seizures, and gut microbiota. This systematic review and meta-analysis explores the alterations of GM composition in patients with epilepsy.

A systematic search was conducted up to June 26, 2024, across PubMed, Scopus, Web of Science, and Embase. The study outcomes were α- and β-diversity indexes, and relative abundance at different bacterial taxonomic levels, compared between epilepsy patients and healthy controls. Inverse variance-weighted meta-analysis was performed to estimate the standardized mean difference. We utilized the Newcastle-Ottawa Scale (NOS) to assess the quality of the included studies.

In this systematic review, we included 16 case-control studies encompassing 438 cases and 369 controls, and 12 studies were included in the meta-analyses. α-diversity was not significantly different between epilepsy and control group. Of the 11 studies measuring β-diversity, 8 studies showed that the microbiota compositions of the two groups differed significantly. Verrucomicrobia was significantly higher in the epilepsy group (SMD = 0.39 [0.05, 0.72], p = 0.022) than in the control group. At the genus level, Roseburia (SMD = -0.50 [-0.84, -0.17], p = 0.003), Blautia (SMD = -0.40 [-0.73, -0.06], p = 0.022), and Dialister (SMD = -0.40 [-0.74, -0.07], p = 0.018) were significantly less abundant in patients with epilepsy.

Our findings evince remarkable changes in gut microbiota composition in epilepsy. Bacterial genera that promote neuroinflammation are elevated in epilepsy. Our study revealed the interrelation between GM disruption and epileptogenesis, but the heterogeneity among the included results was high, and further investigation is encouraged.

Side effects from antiseizure medication (ASM) are common in epilepsy but biomarkers for detection and monitoring are missing. This study investigated associations between CNS-related side effects from ASM and blood concentrations of the brain injury markers neurofilament-light (NFL), total tau, glial acidic fibrillary protein (GFAP), S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE).

This is a population-based cohort study of adults with epilepsy recruited from five Swedish outpatient neurology clinics from December 2020 to April 2023. Side effects classified as CNS-related: tiredness, dizziness, headache, concentration, memory, mood, motor/tremor, or sleep. Marker concentrations in the groups CNS side effects/no side effects were analyzed with Mann-Whitney U-test and significant differences were included in multivariable logistic regression models adjusting for age, epilepsy duration, seizure status, acquired structural lesion, and mono-/polytherapy.

The cohort consisted of 367 patients, 187 (51 %) were females, the median age was 43 years (IQR 30-61), and 123 (34 %) reported CNS side effects. Total tau was higher among participants reporting CNS side effects (median 4.44 (95 %CI 4.12-4.88) pg/ml) compared with participants without side effects (3.84 (95 %CI 3.52-4.07) pg/ml, p < 0.01). The difference remained significant in multivariable regression models. NSE was higher among participants without side effects but did not remain significant in the multivariable regression model. No differences were observed for NFL, GFAP or S100B.

Higher total tau plasma concentration could be associated with increased risk of CNS side effects from ASM. Longitudinal studies could determine if this reflects vulnerability or detrimental effects of ASM.

PREDICT, clinicaltrials.gov identifier NCT04559919.

One of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression omnibus series (GSE) 33000 and GSE63808 datasets were used to search for differentially expressed disulfidptosis-related molecules (DE-DRMs). A correlation between the DE-DRMs was discovered. Individuals with epilepsy were then used to investigate molecular clusters based on the expression of DE-DRMs. Following that, the best machine learning model which is validated by GSE143272 dataset and predictor molecules were identified. The correlation between predictive molecules and clinical traits was determined. Based on the in vitro and in vivo seizures models, experimental analyses were applied to verify the DE-DRMs expressions and the correlation between them. Nine molecules were identified as DE-DRMs: glycogen synthase 1 (GYS1), solute carrier family 3 member 2 (SLC3A2), solute carrier family 7 member 11 (SLC7A11), NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), 3-oxoacyl-ACP synthase, mitochondrial (OXSM), leucine rich pentatricopeptide repeat containing (LRPPRC), NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), NUBP iron‑sulfur cluster assembly factor, mitochondrial (NUBPL), and NCK associated protein 1 (NCKAP1). NDUFS1 interacted with NDUFA11, NUBPL, and LRPPRC, while SLC3A2 interacted with SLC7A11. The optimal machine learning model was revealed to be the random forest (RF) model. G protein guanine nucleotide-binding protein alpha subunit q (GNAQ) was linked to sodium valproate resistance. The experimental analyses suggested an upregulated SLC7A11 expression, an increased number of formed SLC3A2 and SLC7A11 complexes, and a decreased number of formed NDUFS1 and NDUFA11 complexes. This study provides previously undocumented evidence of the relationship between disulfidptosis and EP. In addition to suggesting that SLC7A11 may be a specific DRM for EP, this research demonstrates the alterations in two disulfidptosis-related protein complexes: SLC7A11-SLC3A2 and NDUFS1-NDUFA11.

The limited efficacy and very restricted antiseizure range of current deep brain stimulation (DBS) targets highlight the need to find an optimal target for managing various seizure types. Here, we aimed to investigate the efficacy of DBS on the ventromedial hypothalamus (VMH) in the different types of experimental epileptic seizures.

The efficacy of DBS was examined in various epileptic seizure models, and the potential mechanisms were investigated by using in vivo calcium signal recording and optogenetics.

The c-fos expression was significantly increased in the glutamatergic neurons of VMH (VMHglu) following seizures. Then, 1-Hz low-frequency stimulation (LFS) at the VMH successfully attenuated the seizure severities across models of epilepsy, including the maximal electroshock, the pentylenetetrazol, the absence seizure, the cortical or hippocampal kainic acid-induced acute seizure, and the hippocampal-kindling models. The in vivo calcium imaging recordings revealed that LFS could inhibit the activities of the VMHglu. Optogenetic inhibition of VMHglu mirrored LFS's antiseizure impact. Further anterograde viral tracing confirmed the extensive distributed projections of VMHglu, which may compose the circuitry basis of the broad-spectral efficacy of LFS.

These findings demonstrate that VMH-LFS is a broad-spectrum treatment approach for different seizure types by decreasing VMHglu activity.

Our study aimed to evaluate the effectiveness and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for treating mild to moderate depression in patients with epilepsy (PWE).

A single-arm, prospective, multi-center, pre-post controlled study was conducted in Eastern China. After a four-week baseline period, PWE with mild to moderate depression began treatment with taVNS, administered for 30 min, three times daily, over a 12-week period. The primary outcome measure was the change in 24-item Hamilton Depression Rating Scale (HAMD) scores from baseline to week 12. Secondary outcomes included the response and remission rates for depression at week 12, as well as changes in the 14-item Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) scores, and seizure frequency at weeks 4 and 12 compared to baseline. Adverse events (AEs) were recorded to assess the safety of taVNS. Both modified Intention-To-Treat (mITT) and Per-Protocol (PP) analyses were employed.

Sixty-nine participants were enrolled in this study. Of these, 61 (88.4 %) completed the 4-week treatment phase, and 50 (72.5 %) finished the 12-week treatment phase. In the mITT analysis, HAMD scores significantly decreased by 4.54 ± 7.44 (p < 0.001) from baseline to week 12, with clinical response in 16 (26.2 %) and remission in 15 (24.6 %) patients. HAMA scores also decreased significantly by week 4 (3.23 ± 5.18, p < 0.001) and week 12 (4.95 ± 6.78, p < 0.001). PSQI scores and seizure frequency showed non-significant changes at week 4, but seizure frequency decreased significantly by week 12 (0.03 ± 10.47, p = 0.038). In the PP analysis, similar improvements were observed. After 12 weeks of taVNS compared to baseline, HAMD scores decreased significantly by 5.32 ± 8.98 (p < 0.001), with 32 % of patients achieving a clinical response and 24 % achieving clinical remission. And HAMA scores also decreased by 5.66 ± 7.54 (p < 0.001), seizure frequency by 0.14 ± 11.03 (p = 0.018), and PSQI scores by 1.06 ± 4.14 (p = 0.076).There was a significant increase in QOLIE-31 scores by 5.17 ± 14.71 (p = 0.020). Ten (14.5 %) patients experienced non-serious adverse events, the most common of which was ear pain (n = 4); one patient withdrew due to tinnitus enhancement; all resolved after reducing the stimulation intensity or stopping the treatment.

Our study suggests that taVNS may effectively improve depressive symptoms in PWE. This may be an efficacious and safe treatment for mild to moderate depression in PWE.

This article reviews the comorbidities of epilepsy and identifies tools to incorporate comorbidity awareness into clinical practice.

The comorbidities of epilepsy are broadly defined, including conditions that may cause but also be a consequence of epilepsy. These can be divided into somatic and psychiatric conditions. Many conditions occur twice as frequently in people with epilepsy compared with the general population. The comorbidities of epilepsy are a major determinant of quality of life and mortality in people with epilepsy. This article provides a concerted focus on the relationship between epilepsy and cognition, mental health disorders, and cardiovascular disease.

There are practical means of adopting a comorbidity-aware approach to clinical care without overburdening already busy clinical practices. Screening instruments can be used to identify people with comorbid anxiety or depression. Fundamental safety precautions are relevant to all people with epilepsy. Appropriate consideration of the comorbidities of epilepsy, particularly when choosing an antiseizure medication, leads to improved patient care.

Objective: In patients with epilepsy, the insula has been increasingly recognized as a common site of seizures. There is growing interest in understanding the cognitive and psychological consequences of insular epilepsy to help provide clinical recommendations to support patient's cognitive and psychosocial functioning, and to help identify candidates for epilepsy resective surgery. The aim of this scoping review was to describe the cognitive and behavioural characteristics associated with insular epilepsy in children and adults. Method: A systematic search was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis -Extension for Scoping Reviews guidelines. Eligible studies reported on a neuropsychological or behavioural outcome, using standardized or research-based psychological measures, in individuals with insular epilepsy, (i.e. the seizure focus and/or surgical resection included the insula), and a comparison group. After duplicates were removed, 2,423 citations were identified from the search, and 39 studies were included in the scoping review. Results: Across the included studies, intellectual/global cognitive functioning and language were most often evaluated. Lower functioning was found across multiple cognitive and behavioural processes in pediatric and adult patients with insular epilepsy. Following resective surgery involving the insula, behavioural and cognitive outcomes are general stable. Conclusions: The results of this scoping review further neuropsychologists' knowledge of the cognitive and behavioural outcomes of insular seizures prior to and following surgical treatment. These results can aid in counselling patients of the potential cognitive dysfunctions, and aid with treatment planning.

Epilepsy is a chronic neurological disorder with a burden of comorbidities. Knowledge regarding sarcopenia prevalence and associated risk factors in patients with epilepsy remains limited, which prompted us to conduct the present study.

This cross-sectional study enrolled patients with epilepsy from our epilepsy clinic and controls from the staff at National Cheng Kung University Hospital, Tainan, Taiwan. Sarcopenia was defined using the criteria outlined by the 2019 Asian Working Group for Sarcopenia and the 2010 European Working Group on Sarcopenia in Older People. Muscle mass (skeletal muscle mass index) was measured through bioelectrical impedance, muscle strength was assessed using hand grip tests, and physical performance was evaluated using the 6-m walk test. Hormone (testosterone, growth hormone, and insulin-like growth factor-1) and vitamin D levels were measured. Descriptive statistics and logistic regression models were used to estimate the prevalence of sarcopenia and identify sarcopenia risk factors in patients with epilepsy.

This study enrolled 300 adults (mean age: 42.9 ± 14.7 years; women: 53.7 %). The epilepsy and control groups comprised 200 and 100 participants, respectively. The overall prevalence of sarcopenia was 31.3 % and it was significantly higher (p = 0.004) in women (20.7 %) than in men (10.6 %). The prevalence was higher in the epilepsy group than in the control group (36.0 % vs. 22.0 %, p = 0.014). Logistic regression revealed female, age (≥ 65 year) and low body mass index (BMI) were influenced the risk of sarcopenia in all participants. Importantly, epilepsy is significantly associated sarcopenia. The BMI, protein level, calf circumference, and use of enzyme-inducing antiseizure medications (EIASM) influenced the risk of sarcopenia in the epilepsy group.

The prevalence of sarcopenia is significantly higher in patients with epilepsy than in the control participants. Low BMI, protein level, calf circumference, and the use of EIASM may increase the risk of sarcopenia in this population. Our findings underscore the need for mitigating sarcopenia risk in patients with epilepsy.

Epilepsy impacts cognition during wakefulness. As epileptic activity is present and even augmented during sleep, epilepsy could also influence sleep-related cognitive processes. However, whether epilepsy modulates sleep-related experiences like dreaming remains poorly known. Here, we prospectively investigated the characteristics and determinants of dreaming in patients with epilepsy. Consecutive adult patients with epilepsy and no major cognitive deficit were recruited in an epilepsy outpatient clinic. They completed a questionnaire about their dreams, sleep and epilepsy over the past year. Medical data on epilepsy characteristics were gathered from the medical file. A generalised linear model was used to explore the determinants of dream recall frequency (DRF). We included 300 patients, with a mean (standard deviation [SD]) age of 40.4 (13.4) years and 51.3% female; 28.6% had more than one seizure/month, and 34.7% already had seizures during sleep. Patients recalled dreams on an average of 1.6 (1.5) days/week and 11% had one or more nightmare/week. Younger age, higher number of nocturnal awakenings, and lower seizures frequency predicted a higher DRF. In patients with focal epilepsy (65.3%), the localisation of the epileptic focus in the parieto-occipital area was negatively associated with DRF. Regarding dream content, 34.0% of patients reported having already dreamt about epilepsy. Dreams of seizures were associated with sleep-related seizures (p = 0.034) and dreams of epilepsy were associated with nightmare frequency (p = 0.004). Our results show that patients with epilepsy share several determinants of DRF (age, awakenings, role of the parieto-occipital area) with healthy subjects. In addition, epilepsy-related factors (seizure frequency, focus localisation) also impact DRF. Investigating dreams in patients with epilepsy can provide information on their epilepsy and their sleep.

Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30-50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities -synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE.

The aim of the study was to evaluate the concomitant psychiatric disorders of anxiety and depression in patients with epilepsy caused by low-grade brain tumors (LBTs). We retrospectively reviewed the clinical data of patients who underwent preoperative neuropsychological evaluations of anxiety and depression and subsequent epilepsy surgery for LBTs. The univariate and multivariate analyses were conducted to analyze the risk factors of the occurrence of anxiety and depression. Of the 107 patients included in the study, 42 patients (39.3%) were female, and 28 patients (26.2%) were children. The median age at surgery was 22 years (interquartile range [IQR]: 17-27 years old), the median age of seizure onset was 12 years (IQR: 6-18 years old), and the median duration of epilepsy was 84 months (IQR: 42-180 months). In total, 21 patients (19.6%) had psychiatric disorders of anxiety, and 26 patients (24.3%) had psychiatric disorders of depression. Through univariate and multivariate analysis, discordant (vs. concordant) interictal electroencephalogram (EEG) findings were found to be related to the presence of anxiety (P = 0.035, odds ratio [OR] = 3.35). Discordant (vs. concordant) ictal EEG findings (P = 0.015, OR = 4.44) and temporal location of tumor (P = 0.015, OR = 13.52) were found to be associated with the presence of depression. Psychiatric disorders of anxiety and/or depression could frequently occur in patients with epilepsy caused by LBTs. Thus, early screening and mental intervention are necessary, especially for those with discordant or wider epileptic discharges and temporal invasion of tumors.

Interest in anti-seizure properties of cannabinoids is increasing, with the rise in prevalence of recreational and medical cannabis use, especially across Canada. In a recent study on people with epilepsy (PWE), cannabis use showed a strong association with poor psychosocial health. Sleep and mood comorbidities are highly prevalent in epilepsy, and are common motivations for cannabis use. The primary objective of this study was to assess demographic, subjective and objectively assessed sleep quality and mood related differences among PWE who regularly use cannabis compared to those who do not.

Consecutive consenting patients with a confirmed epilepsy diagnosis, admitted to our Epilepsy Monitoring Unit, over a 3-year period (2019-2022) were enrolled. Detailed epilepsy-related data and self-reported sleep [Pittsburgh Sleep quality index (PSQI)], Epworth Sleepiness Scale (ESS)], mood [(Beck's Depression Inventory (BDI) and Beck's Anxiety inventory (BAI)] and cannabis use related data were collected. Overnight polysomnography (PSG) was conducted on the first night of admission, with simultaneous 18-channel video-EEG. Sleep (PSG) scoring followed American Academy of Sleep Medicine guidelines by a scorer blinded to clinical details.

Among 51 patients with similar seizure control, 25 (13 F) reported cannabis use (mean age 36.3+14.8 years) and were significantly younger than 26 (18 F) non-users (mean age 48.3+15 years). Cannabis users had significantly better subjective sleep quality (mean PSQI scores 7.2+2.9 vs 10.2+5.2 respectively). Most patients endorsed sleepiness (Cannabis users with ESS scores greater than 10; 91.3 %, 77.3 % in non-users) and moderate to extreme depression (BDI) scores. No significant differences were observed in objective sleep parameters. BDI score significantly predicted PSQI and ESS scores on multiple logistic regression analysis.

Despite a significant age difference, self-reported sleep quality is better among PWE who report regular cannabis use compared to non-users. However, there is no significant difference in objective sleep quantity and quality from PSG between the two groups. Additionally, severity of depressive symptoms is a significant predictor of sleep quality and of excessive daytime sleepiness among PWE.

Epilepsy is a chronic condition that confers social stigma, reduced engagement in work and social activities, increased risks of comorbidities, and premature death. It is often treated with medications, but in about a third of patients, epilepsy may be refractory to medications. It is estimated that each year 211,456 new individuals across Africa meet criteria for surgically treatable epilepsy, and the current volume of surgically treatable epilepsy is 1,819,067 cases across the region. Here, we review previously published epilepsy surgery programs in Africa, noting their outcomes.

Eligible studies reporting seizure freedom and/or quality of life outcomes after epilepsy surgeries conducted in Africa were identified through database searches on PubMed/MEDLINE, Google Scholar, and reviewing references in previously identified publications.

While more than a thousand articles were retrieved in the database search, 17 full-length articles were reviewed for eligibility, and 8 articles (likely representing 7 unique patient cohorts) were ultimately included in this study. The reviewed studies demonstrated successful implementation of programs to evaluate patients with epilepsy for surgical treatment. About 60-100% of patients in these cohorts achieved good seizure freedom outcomes within a year from surgery and secondarily had improved quality of life and reduced severity of depression.

This review demonstrates that it is feasible to establish and sustain epilepsy surgery programs in Africa, with seizure freedom outcomes comparable to those reported in studies conducted in parts of the world with higher income.

To investigate phenotypes of comorbidity before and after an epilepsy diagnosis in a national cohort of post-9/11 Service Members and Veterans and explore phenotypic associations with mortality.

Among a longitudinal cohort of Service Members and Veterans receiving care in the Veterans Health Administration (VHA) from 2002 to 2018, annual diagnoses for 26 conditions associated with epilepsy were collected over 5 years, ranging from 2 years prior to 2 years after the year of first epilepsy diagnosis. Latent class analysis (LCA) was used to identify probabilistic comorbidity phenotypes with distinct health trajectories. Descriptive statistics were used to describe the characteristics of each phenotype. Fine and Gray cause-specific survival models were used to measure mortality outcomes for each phenotype up to 2021.

Six distinct phenotypes were identified: (1) relatively healthy, (2) post-traumatic stress disorder, (3) anxiety and depression, (4) chronic disease, (5) bipolar/substance use disorder, and (6) polytrauma. Accidents were the most common cause of death overall, followed by suicide/mental health and cancer, respectively. Each phenotype exhibited unique associations with mortality and cause of death, highlighting the differential impact of comorbidity patterns on patient outcomes.

By delineating clinically meaningful epilepsy comorbidity phenotypes, this study offers a framework for clinicians to tailor interventions. Moreover, these data support systems of care that facilitate treatment of epilepsy and comorbidities within an interdisciplinary health team that allows continuity of care. Targeting treatment toward patients with epilepsy who present with specific heightened risks could help mitigate adverse outcomes and enhance overall patient care.

In this study, we aimed to assess the long-term outcome of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE).

A retrospective analysis of outcome data of 24 patients with DRE, who had been implanted with VNS and had at least 5 years of post-surgery follow-up was performed. The seizure outcome at the latest follow-up was classified as class I-V as proposed by John C. McHugh. The cognitive, psychiatric, and behavioral outcomes were recorded using standardized tests.

Mean age at the time of VNS implantation was 18.7 (6-38) years; nine (37.5%) of the patients were females. Mean duration of epilepsy was 13.6 years (range: 2.5-35 years); 18 (75%) patients had multiple (≥2) seizure types and 15 (62.5%) had daily seizures. The most common etiology was perinatal hypoxic injury (15, 62.5%). More than 50% seizure reduction (class 1 and 2) was noted in 54.2% of patients at 1 year, which increased to 75% at ≥5 years follow-up. A significantly higher number of patients with other etiologies had >50% reduction in seizures at the latest follow-up, when compared to those with hypoxic-ischemic encephalopathy (53.3% vs. 100%, P = 0.0024). The average intelligence quotient (IQ; 71.17 ± 28.92 vs. 64.65 ± 29.61, P = 0.014) and quality of life (66.64 ± 14.63 vs. 64.65 ± 29.61, P < 0.001) scores were significantly higher in patients post-VNS implantation, when compared to their baseline scores. Furthermore, significant number of patients had improvement in psychiatric diagnosis (29.2% vs. 4.2%, P = 0.047) and behavioral problems (50% vs. 4.2%, P < 0.001) post-VNS implantation.

The present study shows >50% seizure reduction in 75% of patients after VNS implantation at long-term follow-up, with improvement in IQ, quality of life, psychiatric and behavioral problems.

Targeted Recombination in Active Populations (TRAP) represents an effective and extensively applied technique that has earned significant utilization in neuroscience over the past decade, primarily for identifying and modulating functionally activated neuronal ensembles associated with diverse behaviors. As epilepsy is a neurological disorder characterized by pathological hyper-excitatory networks, TRAP has already been widely applied in epilepsy research. However, the deployment of TRAP in this field remains underexplored, and there is significant potential for further application and development in epilepsy-related investigations. In this review, we embark on a concise examination of the mechanisms behind several TRAP tools, introduce the current applications of TRAP in epilepsy research, and collate the key advantages as well as limitations of TRAP. Furthermore, we sketch out perspectives on potential applications of TRAP in future epilepsy research, grounded in the present landscape and challenges of the field, as well as the ways TRAP has been embraced in other neuroscience domains.

Epilepsy, as a chronic noncommunicable disease with recurrent seizures, may be a marker of deterioration or alteration in other underlying neurological diseases. This study aimed to investigate the relationship of epilepsy with brain function, other common brain disorders, and their underlying mechanisms.

The study was based on clinical diagnostic and test data from 426,527 participants in the UK Biobank, of whom 3,251 were diagnosed with epilepsy at baseline. Multiple linear and Cox regression models were used to explore the association between epilepsy, brain function, and other brain disorders.

This study demonstrated consistent deleterious effects of epilepsy on cognitive and motor function and mental health. The risk of neurological diseases and psychiatric disorders was significantly elevated in the epilepsy population during the 17-year follow-up period, according to the longitudinal analysis. We also identified several brain regions associated with epilepsy, including the pallidum, hippocampus, and precentral regions. Mediation analyses revealed mediating effects of peripheral markers and proteins (e.g., GGT, HDL, ACE2, and GDF15), suggesting that liver function and lipid metabolism may be involved in the development of other brain disorders in individuals with epilepsy.

Our study provides robust evidence of the association between epilepsy and poor brain health, underscoring the importance of early intervention for epilepsy.

Initiation and maintenance of antiseizure therapy can be relatively straightforward in most patients. Depending on epilepsy type, patients may be more or less likely to enter remission or a resolution of their epilepsy and the International League Against Epilepsy developed clinically guiding definitions in this regard. The mechanisms by which resolution or remission are achieved are poorly understood which complicates clinical decision making and risk estimate for future seizure relapse. The impetus for the maintenance of medical therapy in a seizure-free patient is also age-dependent. In children, one ought to consider the unknown effects of antiseizure medications on the developing brain while family planning, lifestyle, education, or employment are some of the issues that affect the decision making in adults. Patients who enter remission following surgical remediation of their epilepsy represent a distinct category and medication discontinuation is influenced by a number of factors. Another important consideration is comorbidities that often affect medication choices and maintenance. When formulating a management strategy, patient preferences together with careful evaluation and precise and accurate epilepsy diagnosis are key towards guiding medical or surgical management, prognostication for seizure freedom, relapse risk, options for medication discontinuation, and understanding risks and types of comorbidities.

While it is known that epilepsy often co-occurs with psychiatric disorders, few studies have examined nonpsychiatric comorbidity. We analyzed 2021 and 2022 National Health Interview Survey Sample Adult data. Compared with adults with no epilepsy, the 1.2% of US adults (about 3.0 million) with active epilepsy had a higher prevalence of nearly all 21 conditions examined and were more likely to have 4 or more co-occurring chronic conditions. Health care and social service providers can promote healthy behaviors and preventive screening for common comorbidities, improve access to care, and refer people with epilepsy to evidence-based self-management programs.

Epilepsy is a chronic neurological disorder characterized by repetitive unprovoked seizures. While certain anti-seizure medications have been linked to urinary tract infections, limited information exists on the occurrence and risk factors of asymptomatic bacteriuria (ASB) in individuals with epilepsy. This study aims to investigate the prevalence and factors associated with ASB in patients with epilepsy.

A cross-sectional study was conducted, enrolling patients with epilepsy and healthy adults as controls. All participants underwent urine analyses during follow-ups at an epilepsy special clinic. Data on epilepsy-related factors were thoroughly collected and analyzed. Descriptive statistics and a logistic regression model were employed to identify the prevalence and risk factors of ASB in patients with epilepsy.

The study encompassed 200 patients with epilepsy, compared to 100 healthy controls. The prevalence of ASB in the epilepsy group was significantly higher than in the healthy controls (34.0 % versus 16.2 %, p = 0.001). The logistic regression model identified factors statistically associated with ASB in epilepsy, including gender (female) (p < 0.001), proteinuria (p = 0.021), and the use of oxcarbazepine (p = 0.011). Interestingly, lamotrigine demonstrated a protective effect against ASB (p = 0.023), along with age (p = 0.015) in this study. Moreover, patients with and without ASB exhibited a similar rate of 12 months of seizure freedom.

The prevalence of ASB is elevated in epilepsy, with identified risk factors including gender (female), proteinuria, and the use of the anti-seizure medication oxcarbazepine. Lamotrigine was found to be protective. These findings underscore the importance of clinician awareness, and careful monitoring of anti-seizure medication therapy.

Depression is one of the most common mental disorders and is associated with a significant increase in the risk of mental and somatic comorbidities. The chronobiological theory of the pathogenesis of depression explains the relationship between the symptoms of depression and disturbance of circadian rhythm regulation. Disrupted circadian rhythms are also observed in other disorders such as alcohol use disorder, anxiety disorders, epilepsy, and Parkinson's disease. Therefore, there is a growing interest in the use of medications with a melatoninergic mechanism of action in the treatment of depression comorbid with the aforementioned disorders.

This review aims to systematically examine the evidence for the use of melatoninergic antidepressants (agomelatine and fluvoxamine) in the treatment of depression comorbid with alcohol abuse, anxiety disorders (including phobic anxiety, panic, and generalized anxiety disorders), or neuropsychiatric disorders (such as epilepsy and Parkinson's disease).

This systematic review included experimental studies, systematic reviews, and meta-analyses published in English and Russian, which examined the use of fluvoxamine and agomelatine in adult patients with recurrent depressive disorder (ICD-10) or major depressive disorder (DSM-5) comorbid with alcohol abuse, anxiety or neuropsychiatric disorders. The search was conducted in the PubMed, Cochrane Library and eLIBRARY scientific databases. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool, which is used to evaluate the risk of systematic errors in clinical studies. The results were presented as a narrative synthesis and grouped by the comorbidities evaluated.

A total of 20 articles were reviewed (with a pooled sample size of n=1,833 participants). The results suggest that melatoninergic antidepressants might help in reducing depressive and anxiety symptoms, improve sleep, decrease alcohol cravings, and alleviate the severity of motor symptoms in Parkinson's disease. Moreover, the use of pharmacogenetic testing to select the medication and dosage may enhance its therapeutic effectiveness.

The review demonstrates a significant lack of clinical data and guidelines on the use of melatoninergic medications for the treatment of depression comorbid with other disorders. In this regard, it is currently difficult to draw a definitive conclusion regarding the efficacy and safety of agomelatine and fluvoxamine in the treatment of these comorbidities. Available studies suggest an improvement in the clinical manifestations of the comorbidities. Future research directions might include the development and implementation of double-blind, randomized clinical trials to study the use of melatoninergic medications in patients with depression comorbid with other disorders.

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 encoding a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

Epilepsy and migraine without aura (MWoA) are often comorbid, but the exact mechanisms are unclear. Magnetic resonance spectroscopy (1H-MRS) may help to understand the neurometabolic mechanisms in patients with epilepsy comorbid with MWoA (EWM). In this prospective cross-sectional study, we recruited 64 female patients, including 24 with EWM, 20 with epilepsy, and 20 with MWoA, as well as 20 age-level-matched and educational-level-matched female healthy controls from our hospital between August 2021 and November 2022. A single-voxel point-resolved spectroscopy sequence was used to acquire spectra of the bilateral dorsolateral prefrontal cortices (DLPFCs). Metabolites were quantified by linear combination model software, and the values were corrected for the partial volume effect of cerebrospinal fluid. MRS data comparisons were performed with multivariate analyses of variance. Correlation analyses were calculated between metabolites and main clinical data. The results showed that N-acetyl aspartate (NAA) was asymmetrical between the bilateral DLPFCs. Both NAA and myoinositol were significantly reduced in EWM than in healthy controls. Choline-containing compounds (Cho) were higher in MWoA than in the other three groups. Correlation analyses revealed that NAA of the right DLPFC and Cho of the bilateral DLPFCs in EWM were negatively related to migraine frequency. In addition, glutamate and glutamine (Glu and Gln, Glx) of the right DLPFC in EWM were negatively correlated with migraine severity. Our findings suggested that comorbid epilepsy and MWoA in female patients can lead to a synergistic reduction of both NAA and myoinositol, reflecting more serious injuries of neurons and glial cells.

Epilepsy is a common brain function disorder. The present study aims to evaluate the long-term effect of perampanel (PRM) and lacosamide (LCM), administered singly in a high-dose or in a low-dose combination of both, on comorbid anxiety, cognitive impairment, BDNF, and Cyclin D1 hippocampal expression in an experimental model of temporal lobe epilepsy with lithium-pilocarpine. PRM (3 mg/kg, p.o.)/LCM (30 mg/kg, p.o.) or PRM+LCM (0.5 mg/kg + 3 mg/kg, p.o.) treatments were administered three hours after the lithium-pilocarpine-induced status epilepticus and continued for up to ten weeks in adult Wistar rats. Our study demonstrated that perampanel and lacosamide administered singly in high doses improved epilepsy-associated cognitive impairment through ameliorating anxiety and facilitating passive learning and memory, with spatial and recognition memory measured in the elevated plus maze, step-through, Y-maze, and object recognition tests, respectively. In addition, the combination of both drugs in low doses demonstrated similar anxiolytic and cognitive-improving effects compared to the singly administered drugs. Moreover, the three experimental groups enhanced the hippocampal expression of the neurotrophic factor BDNF and mitigated the increased levels of the apoptotic factor Cyclin D1. These beneficial effects could be essential mechanisms through which administered anticonvulsants preserve neuronal survival and homeostasis in the CNS and especially in the hippocampus.

Seizures and epilepsy can be debilitating neurological conditions and have few known causes. Emerging evidence has highlighted the potential contribution of environmental exposures to the etiology of these conditions, possibly manifesting via neuroinflammation and increased oxidative stress in the brain. We conducted a scoping review of epidemiological literature linking air pollution and temperature exposures with incidence and acute aggravation of seizures and epilepsy. We systematically searched PubMed, Embase, Web of Science, and APA PsycINFO databases for peer-reviewed journal articles published in English from inception to February 7, 2024.

We identified a total of 34 studies: 16 examined air pollution exposure, 12 ambient temperature, and six examined both air pollution and ambient temperature. Most studies were conducted in Asia (China, Taiwan, South Korea, and Japan). Nearly all studies retrospectively derived acute (daily average), ambient, and postnatal exposure estimates from ground monitoring systems and ascertained epilepsy cases or seizure events through record linkage with medical records, health registry systems, or insurance claims data. Commonly assessed exposures were particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and daily mean ambient temperature. Overall, the main findings across studies lacked consistency, with mixed results reported for the associations of air pollutants and temperature metrics with both seizure incidence and acute aggravations of epilepsy.

While an increasing number of researchers have focused on the correlation between the immune system and epilepsy, the precise causal role of immune cells in epilepsy continues to elude scientific understanding. The aim of the study was to examine the causal relationship between peripheral immune phenotypes and epilepsy.

Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) were utilized to determine the causal relationship between 731 immune cell traits and various types of epilepsy in this study.

LDSC revealed that 80 immunophenotypes showed genetic correlation with epilepsy, including 58 immunophenotypes associated with a single type of epilepsy (72.5 %),14 immunophenotypes associated with two types of epilepsy (17.5 %),7 immunophenotypes with 3 types of epilepsy (8.75 %) and 1 immunophenotype with 5 types of epilepsy (1.25 %). Although none of the types of epilepsy had a statistically significant effect on immunophenotypes, it is noteworthy that the MR revealed the protective effects of five immunophenotypes on epilepsy: CD45RA+CD8br AC (OR:0.86, 95 %CI:0.80-0.93), FSC-A on myeloid DC (OR:0.95, 95 %CI:0.91-0.98）, CM CD8br AC (OR:0.69, 95 %CI:0.59--0.82), CD33 on CD66b++ Myeloid cell (OR:0.88, 95 %CI:0.83-0.93) and CD127 on CD28- CD8br (OR:0.97, 95 %CI:0.95-0.98). Additionally, harmful effects were observed for two immunophenotypes on epilepsy:CD4 Treg %CD4 (OR:1.04, 95 %CI:1.02-1.06) and SSC-A on plasmacytoid DC (OR:1.01, 95 %CI:1.00-1.02).

Our research has demonstrated the causal connections between immune cells and epilepsy, potentially providing valuable insights for future clinical studies.